Cortical systems that participate in object and spatial vision and in working and long-term visual memory were investigated in healthy young men by measuring regional cerebral blood flow (rCBF) with positron emission tomography (PET) and H215O. The results identified dorsolateral occipital and superior parietal areas activated more by spatial visual processing, and ventral occipital and occipitotemporal areas activated more by object discrimination. Old subjects demonstrated rCBF activations in the same regions as did young subjects, but also demonstrated activation of ventral areas during spatial vision and dorsal areas during object vision, suggesting less functional separation of these visual systems. Patients with dementia of the Alzheimer type (DAT) demonstrated normal percent baseline activation of rCBF in occipitotemporal cortex during object vision, suggesting preserved capacity to recruit this area for perceptual processing. Memory-related modulations of cortical rCBF were found in anterior temporal and prefrontal cortex. Neuropsychological decline in very early Alzheimer's disease was found to have an early plateau phase followed by steady, linear decline. Rate of cognitive decline was significantly correlated with rate of brain tissue loss, as measured with serial CT scans, and with rate of worsening abnormality of resting state regional cerebral metabolic rates for glucose (rCMRglc) as measured by PET and 18F-Fluorodeoxyglucose. Cognitive studies of complex attention, the first nonmemory function to demonstrate impairment in early DAT, identified three similar impairments of shifting or divided attention. Older Down syndrome adults perform worse on mental abilities tests than do younger subjects. Immediate memory and language function are less affected by age in Down syndrome than are long-term memory and visuospatial function.